Immunocompromised patients with prolonged COVID-19 symptoms present diagnostic and therapeutic challenges. We measured viral nucleocapsid antigenemia in three patients treated with anti-CD20 immunotherapy who acquired SARS-CoV-2 infection and experienced protracted symptoms. Our results support nucleocapsid antigenemia as a marker of persistent infection and therapeutic response.

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Background Nasopharyngeal qualitative RT-PCR is the gold standard for diagnosis of SARS-CoV-2 infection, but not practical or sufficient in every clinical scenario due to its inability to distinguish active from resolved infection. Alternative or adjunct testing may be needed to guide isolation precautions and treatment in hospitalized patients. Methods We performed a single-center, retrospective analysis of residual clinical specimens and medical record data to examine blood plasma nucleocapsid antigen as a candidate biomarker of active SARS-CoV-2. Adult patients admitted to the hospital or presenting to the emergency department with SARS-CoV-2 RNA detected by RT-PCR from a nasopharyngeal swab specimen were included. Both nasopharyngeal swab and a paired whole blood sample were required to be available for analysis. Findings 54 patients were included. 8 patients had positive nasopharyngeal swab virus cultures of which 7 (87·5%) had concurrent antigenemia. 19 (79·2%) of 24 patients with detectable sub-genomic RNA and 20 (80·0%) of 25 patients with N2 RT-PCR Ct ≤ 33 had antigenemia. Interpretation Most individuals with active SARS-CoV-2 infection are likely to have concurrent antigenemia, but there may be some individuals with active infection in whom antigenemia is not detectable. The potential for high sensitivity and convenience of a blood test prompts interest in further investigation as a screening tool to reduce reliance on nasopharyngeal swab sampling and as an adjunct diagnostic test to aide in clinical decision making during the period following acute COVID-19.